2we6

Crystal Structure of Plasmodium falciparum Ubiquitin Carboxyl- terminal Hydrolase 3 (UCHL3)

spinqualitylabelsall models 2we6, resolution 2.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2we6 is a 2 chain structure with sequence from Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.42Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function UCHL3_PLAF7 Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8 (PubMed:17371404, PubMed:31658303, PubMed:20042598). Essential for parasite blood stage survival (PubMed:20042598). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Like their human hosts, Plasmodium falciparum parasites rely on the ubiquitin-proteasome system for survival. We previously identified PfUCHL3, a deubiquitinating enzyme, and here we characterize its activity and changes in active site architecture upon binding to ubiquitin. We find strong evidence that PfUCHL3 is essential to parasite survival. The crystal structures of both PfUCHL3 alone and in complex with the ubiquitin-based suicide substrate UbVME suggest a rather rigid active site crossover loop that likely plays a role in restricting the size of ubiquitin adduct substrates. Molecular dynamics simulations of the structures and a model of the PfUCHL3-PfNedd8 complex allowed the identification of shared key interactions of ubiquitin and PfNedd8 with PfUCHL3, explaining the dual specificity of this enzyme. Distinct differences observed in ubiquitin binding between PfUCHL3 and its human counterpart make it likely that the parasitic DUB can be selectively targeted while leaving the human enzyme unaffected. Characterization and structural studies of the Plasmodium falciparum ubiquitin and Nedd8 hydrolase UCHL3.,Artavanis-Tsakonas K, Weihofen WA, Antos JM, Coleman BI, Comeaux CA, Duraisingh MT, Gaudet R, Ploegh HL J Biol Chem. 2010 Feb 26;285(9):6857-66. Epub 2009 Dec 30. PMID:20042598 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thioesterase 3D structures

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